Considerable evidence exists to indicate that local hyperthermia, alone, or with radiation or drugs, is of value in the therapy of localized malignant tumors. Uniformity of temperature in the treatment field is, however, necessary to establish accurate temperature-duration relationships for tumor response and elucidation of underlying biological mechanisms. A technique for production of such hyperthermia restricted to the treatment volume, superficial or deep, with sparing of normal tissues was developed utilizing steered, focused ultrasound and was evaluated in experimental animals, and canine and human patients. The results were remarkable in the absence of toxicity and high response rates at heat-dose levels lower than those reported in the literature. The research program proposed represents a multidisciplinary, but orchestrated effort for further evaluation and refinement of different aspects of local hyperthermia as a modality in cancer therapy. Phase I and II trials will be continued in patients with superficial and deep tumors, using hyperthermia alone, or with radiation or drugs. The studies will be extended to genitourinary and other intra-abdominal tumors, and to glioblastoma multiforme after the safety of the procedure is established in animal experiments. Effects of known levels of tumor hyperthermia in situ, such as changes in tumor and tumor-bed blood perfusion, and effects on different cytological parameters will be studied using sensitive techniques and will be correlated with the clinical results. The ultrasponic technique for generation of hyperthermia will be refined for easier clinical use, and alternative approaches using electromagnetic energy will be explored to supplement or complement the ultrasonic technique. Non-invasive methods for measurement of temperature in the target tissue will be evaluated, and a predictive computer model of tissue temperature distribution resulting from a known energy input in tissues of known thermo-physical characteristics will be developed. These developments are expected to make a definitive, long term contribution to the science of local hyperthermia for tumor therapy.